Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors.
Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors.
复制标题
DOI：
10.1155/2015/375349
复制
发表时间：
2015
影响因子：
2.8
通讯作者：
Fallo F
中科院分区：
文献类型：
--
作者：
Pilon C;Rebellato A;Urbanet R;Guzzardo V;Cappellesso R;Sasano H;Fassina A;Fallo F
我们先前显示，维生素D受体（VDR）mRNA/蛋白质在一小群肾上腺皮质癌（ACC）组织中的表达降低，这表明VDR在这种癌症类型中对恶性细胞生长的保护作用丧失。VDR基因表达下调可能是由于表观遗传学事件，即VDR基因启动子区CpG岛胞嘧啶核苷酸甲基化所致。我们分析了正常肾上腺和肾上腺皮质肿瘤样本中VDR基因启动子CpG位点的甲基化。采用亚硫酸氢盐处理的石蜡包埋肾上腺皮质组织DNA，通过亚硫酸氢盐测序PCR评估富含CpG的5′端区域的甲基化。本文对3例正常肾上腺和23例肾上腺皮质肿瘤（腺瘤15例，癌8例）进行了研究。在3/8例ACC中发现VDR基因启动子区甲基化，而在正常肾上腺和肾上腺皮质腺瘤中未发现VDR基因甲基化。ACCs中VDR mRNA和蛋白水平低于良性肿瘤，ACCs中VDR免疫染色较弱或阴性，包括所有3个甲基化组织样本。VDR基因启动子甲基化和VDR基因表达降低之间的关联在ACC中并不罕见，这表明VDR表观遗传失活可能在肾上腺皮质癌发生中起作用。
We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5′ regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis.